RATIONALE:
Vagus nerve stimulation (VNS) is a treatment option in the case of refractory epilepsy. However, several side effects have been reported, including dyspnea, coughing and bradycardias [JCA 2010: 22;213-222]. Although some patients experience hardly any side effects from the stimulation during rest, they mention a decrease in physical condition during exercise is. The experience of a decrease in physical condition during exercise is reported as shortness of breath when the stimulator is on. It is unclear whether this actually has a laryngeal or respiratory cause, or whether there are cardiac or combined causes as well. The aim of this study is to explore the contribution of these various potential causes to the exercise intolerance reported by several patients treated with a VNS device.
METHODS:
In a case controlled observational study, 5 epilepsy patients who report side effects during exercise are compared to 5 patients without side effects and 5 healthy subjects. All subjects are measured during rest and during a non-maximal ergometry test. During these tests, which both take 20 minutes, respiratory parameters (tidal volume, breathing frequency and minute volume), ECG, 32-channel EEG, pulse oximetry and periodic blood pressure (BP) are measured. Epilepsy patients with VNS are asked to activate the device 3 times during the tests, to study the effects of the stimulation on the aforementioned parameters.
RESULTS:
At present, 1 patient with and 1 patient without side effects have been included, as well as 4 healthy subjects. In healthy subjects, stable values for the parameters during rest are observed. During the first few minutes of exercise, heart rate and systolic BP increase, while diastolic BP decreases slightly. Thereafter, a steady state is reached. All values are as expected during exercise. In the patients, the same effect of exercise as in healthy subjects occurs. The stimulation does not influence the BP, saturation and respiratory parameters. Heart rate analysis in both patients showed a small but significant increase in inter-beat intervals during stimulation, indicating a slight decrease in heart rate. This happened during both rest and exercise.
CONCLUSIONS:
Preliminary results show that during stimulation of the vagus nerve, small but reproducible slowing of heart rate occurs. No robust conclusion can yet be drawn about the effect of stimulation on respiratory parameters
Effective treatments to improve brain recovery after cardiac arrest are needed. Ghrelin showed efficacy in experimental models and was associated with lower neuron-specific enolase levels in the clinical Ghrelin in Coma (GRECO) trial. Here, we present cognitive and psychosocial outcomes at 1-year follow-up. GRECO was a Phase 2 multicentre, double-blind, randomized, placebo-controlled trial in comatose patients after cardiac arrest. The intervention was intravenous acyl-ghrelin 600 μg twice daily or placebo for 1 week, starting within 12 h after the arrest. Patients were assessed after 1 year using cognitive tests and questionnaires measuring participation, health-related quality of life, mood, and caregiver strain. Composite z-scores of the cognitive tests were computed by comparing the scores with those of a norm population and averaging the tests for memory, attention, and executive functioning separately. Groups were compared based on composite z-scores and cut-off scores for psychosocial outcomes. Of the 160 participants originally included, 66 of the 85 participants who survived to 1 year after OHCA completed the psychosocial and cognitive follow-up. The intervention group scored numerically higher across the cognitive domains compared with the control group, but the differences were not statistically significant (memory median = -0.850 vs. -1.385, U = 424.5, P = 0.587; attention median = -0.733 vs. -0.717, U = 420.5, P = 0.548; and executive functioning median = -0.311 vs. -0.482, U = 408.5, P = 0.323). There were significantly fewer signs of depression in the intervention group (U = 322.5, P = 0.014). This predefined secondary analysis found that ghrelin treatment was associated with non-significantly but consistently better cognitive outcomes and significantly fewer signs of depression. This is in line with the primary outcomes. Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.
Evaluation of: Chollet F Tardy J, Albucher JF et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 10(2), 123–130 (2011). In this study, the authors examined the effects of administration of fluoxetine for 90 days on the recovery of motor function in acute stroke patients. They found that motor function in the group receiving fluoxetine improved significantly compared with the control group. Before administration of fluoxetine can be used as a new therapeutic treatment to improve the rehabilitation after stroke, the long-term effects in chronic stroke patients, as well as the physiological effects, have to be studied and compared with the results of other neuropharmacalogical agents.
Outcome prediction in patients after cardiac arrest (CA) is challenging. Electroencephalographic reactivity (EEG-R) might be a reliable predictor. We aimed to determine the prognostic value of EEG-R using a standardized assessment.In a prospective cohort study, a strictly defined EEG-R assessment protocol was executed twice per day in adult patients after CA. EEG-R was classified as present or absent by 3 EEG readers, blinded to patient characteristics. Uncertain reactivity was classified as present. Primary outcome was best Cerebral Performance Category score (CPC) in 6 months after CA, dichotomized as good (CPC = 1-2) or poor (CPC = 3-5). EEG-R was considered reliable for predicting poor outcome if specificity was ≥95%. For good outcome prediction, a specificity of ≥80% was used. Added value of EEG-R was the increase in specificity when combined with EEG background, neurological examination, and somatosensory evoked potentials (SSEPs).Of 160 patients enrolled, 149 were available for analyses. Absence of EEG-R for poor outcome prediction had a specificity of 82% and a sensitivity of 73%. For good outcome prediction, specificity was 73% and sensitivity 82%. Specificity for poor outcome prediction increased from 98% to 99% when EEG-R was added to a multimodal model. For good outcome prediction, specificity increased from 70% to 89%.EEG-R testing in itself is not sufficiently reliable for outcome prediction in patients after CA. For poor outcome prediction, it has no substantial added value to EEG background, neurological examination, and SSEPs. For prediction of good outcome, EEG-R seems to have added value. ANN NEUROL 2019.
To establish incidence, phenotype, long-term functional outcome, and early EEG predictors of delirium after cardiac arrest.This is an ad hoc analysis of a prospective cohort study on outcome prediction of comatose patients after cardiac arrest. Patients with recovery of consciousness, who survived until hospital discharge, were subdivided in groups with and without delirium based on psychiatric consultation. Delirium phenotype and medical treatment were retrieved from patient files. All other data were prospectively collected. We used univariate analyses of baseline and early EEG characteristics for identification of possible delirium predictors. Association of delirium with neurological recovery at six months was analyzed with multinomial logistic regression analysis.Of 233 patients, 141 survived until hospital discharge, of whom 47 (33%) were diagnosed with delirium. There were no differences in baseline characteristics between patients with and without delirium. All delirious patients were treated with relatively high dosages of psychopharmaceuticals, mostly haloperidol and benzodiazepine agonists. Prevalent characteristics were disturbed cognition, perception and psychomotor functioning (98%). Half of the patients had language disorders or shouting. Delirium was associated with longer ICU and hospital admission, and more frequent discharge to rehabilitation centre or nursing home. There was a trend towards poorer neurological recovery. EEG measurements within 12 h after cardiac arrest could predict delirium with 91% specificity and 40% sensitivity.Delirium is common after cardiac arrest, and probably leads to longer hospitalization and poorer outcome. Optimal treatment is unclear. Early EEG holds potential to identify patients at risk.
